Delirium is a common psychiatric disorder in the terminally ill (See Fast Fact #1). Delirium can deeply disturb the patient and family; treatment is generally indicated in either a hyperactive or hypoactive delirium. Management options include identifying and treating the underlying cause, as well as symptomatic treatment through non-pharmacological and pharmacological interventions. Common reversible etiologies in advanced terminal illness include drug toxicity, infection, hypotension, hypoxia, hypoglycemia, hyponatremia, hypercalcemia, elevated ammonia, alcohol-sedative drug withdrawal, and sleep deprivation.

With the exception of treating delirium due to drug withdrawal or anticholinergic excess, neuroleptics are the first-line pharmacological agents for symptomatic management. Benzodiazepines should be avoided unless the source of delirium is alcohol-sedative drug withdrawal or when severe agitation is not controlled by the neuroleptic; these agents can cause "paradoxical" worsening of confusional states. The best studied neuroleptic, and the agent of choice for most patients, is haloperidol (Haldol), which has a favorable side effect profile and can be administered safely through oral and parenteral routes. Starting doses are 0.5 - 1.0 mg PO or IM/IV; titration can occur by 2.0 - 5.0 mg every 1 hour until a total daily requirement is established, which is then administered in 2-3 divided doses per day. Intravenous haloperidol may cause less extrapyramidal symptoms than oral haloperidol.

Other neuroleptics are probably comparable to haloperidol in controlling delirium (and many are also good anti-emetics), but may have a higher incidence of side effects: extrapyramidal reactions, sedation, and hypotension. Chlorpromazine (Thorazine) has been advocated for dying patients in whom sedation is desired, especially for terminal delirium.

Newer atypical neuroleptics, olanzapine (Zyprexa), quetiapine (Seroquel), and risperidone (Risperdal) may be helpful in the management of confusional states. Evidence supporting usage of atypical neuroleptics in delirium is scant, so they should not be considered a first-line treatment. However, these agents are associated with fewer drug- induced movement disorders than haloperidol, and may be agents of choice in patients with Parkinson's disease and related neuromuscular disorders, as well as patients with a history of extrapyramidal reactions from neuroleptics.

The starting dose for olanzapine is 5 mg PO every day; after one week, the dose can be raised to 10 mg a day and titrated to 20 mg a day. Quetiapine is initially given 25 mg PO twice a day which can be raised by 25 - 50 mg per dose every 2 - 3 days up to a target of 300 - 400 mg a day, divided into 2 - 3 doses. Risperidone is given 1 - 2 mg PO at night and is gradually raised 1 mg every 2 - 3 days until an effective dose (usually 4 - 6 mg PO hs) is reached. These agents are not available in either intramuscular or intravenous routes.

The switch to an atypical neuroleptic may be made abruptly but it is probably wiser to taper off the typical agent slowly while titrating up the atypical agent. Atypical antipsychotics may not work as fast as conventional antipsychotics for acutely aggressive and agitated patients requiring onset of action within minutes. Quetiapine is the most sedating of the newer agents and has potential applicability in treating agitated delirium, especially at the end of life.

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